Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas
Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladd...
Gespeichert in:
Veröffentlicht in: | Clinical and experimental medicine 2015-08, Vol.15 (3), p.421-426 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the
MYC
and
TP53
copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether
MYC
may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples (
p
= 0.002,
p
= 0.046, respectively). Gain of copies of the
MYC
and
TP53
genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively.
MYC
and
TP53
amplifications were associated with immunoreactivity of their protein (
p
= 0.029,
p
= 0.001, respectively).
MYC
hypomethylation was only detected in tumoral samples and was associated with its protein expression (
p
= 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors (
p
= 0.019) and with MYC expression (
p
= 0.044). Moreover, two tumors presented a pathogenic mutation in
MYC
exon 2 (rs28933407). Our study highlights that the gain of
MYC
and
TP53
copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at
MYC
may contribute to overexpression of its protein in this type of cancer. |
---|---|
ISSN: | 1591-9528 1591-8890 1591-9528 |
DOI: | 10.1007/s10238-014-0311-8 |